Microbial stimulation fully differentiates monocytes to DC-SIGN/CD209(+) dendritic cells for immune T cell areas.

Dendritic cells (DCs), critical antigen-presenting cells for immune control, normally derive from bone marrow precursors distinct from monocytes. It is not yet established if the large reservoir of monocytes can develop into cells with critical features of DCs in vivo. We now show that fully differentiated monocyte-derived DCs (Mo-DCs) develop in mice and DC-SIGN/CD209a marks the cells. Mo-DCs are recruited from blood monocytes into lymph nodes by lipopolysaccharide and live or dead gram-negative bacteria. Mobilization requires TLR4 and its CD14 coreceptor and Trif. When tested for antigen-presenting function, Mo-DCs are as active as classical DCs, including cross-presentation of proteins and live gram-negative bacteria on MHC I in vivo. Fully differentiated Mo-DCs acquire DC morphology and localize to T cell areas via L-selectin and CCR7. Thus the blood monocyte reservoir becomes the dominant presenting cell in response to select microbes, yielding DC-SIGN(+) cells with critical functions of DCs.

Comparative genomics reveals insights into the potential of Lysinibacillus irui as a plant growth promoter.

Members of the genus Lysinibacillus attract attention for their mosquitocidal, bioremediation, and plant growth-promoting abilities. Despite this interest, comprehensive studies focusing on genomic traits governing plant growth and stress resilience in this genus using whole-genome sequencing are still scarce. Therefore, we sequenced and compared the genomes of three endophytic Lysinibacillus irui strains isolated from Canary Island date palms with the ex-type strain IRB4-01. Overall, the genomes of these strains consist of a circular chromosome with an average size of 4.6 Mb and a GC content of 37.2%. Comparative analysis identified conserved gene clusters within the core genome involved in iron acquisition, phosphate solubilization, indole-3-acetic acid biosynthesis, and volatile compounds. In addition, genome analysis revealed the presence of genes encoding carbohydrate-active enzymes, and proteins that confer resistance to oxidative, osmotic, and salinity stresses. Furthermore, pathways of putative novel bacteriocins were identified in all genomes. This illustrates possible common plant growth-promoting traits shared among all strains of L. irui. Our findings highlight a rich repertoire of genes associated with plant lifestyles, suggesting significant potential for developing inoculants to enhance plant growth and resilience. This study is the first to provide insights into the overall genomic signatures and mechanisms of plant growth promotion and biocontrol in the genus Lysinibacillus. KEY POINTS: • Pioneer study in elucidating plant growth promoting in L. irui through comparative genomics. • Genome mining identified biosynthetic pathways of putative novel bacteriocins. • Future research directions to develop L. irui-based biofertilizers for sustainable agriculture.

COVID-19 vaccination uptake for half a million non-EU migrants and refugees in England: a linked retrospective population-based cohort study.

BACKGROUND: COVID-19 has highlighted severe health inequities experienced by certain migrants. Despite evidence suggesting that migrants are at risk of under-immunisation, data are limited for migrants' COVID-19 vaccine uptake in England. METHODS: We did a retrospective population-based cohort study on COVID-19 vaccination uptake in England. We linked the Million Migrant cohort (which includes non-EU migrants and resettled refugees) to the national COVID-19 vaccination dataset, using a stepwise deterministic matching procedure adapted from NHS Digital, and compared migrants with the general population. For migrants who linked to at least one vaccination record, we estimate temporal trends in first dose uptake and differences in second and third dose uptake and consequent delays between Dec 8, 2020, and April 20, 2022, by age, visa type, and ethnicity. FINDINGS: Of the 465 470 migrants who linked to one or more vaccination record, 427 073 (91·8%) received a second dose and 238 721 (51·3%) received a third. Migrants (>30 years) reached 75% first-dose coverage between 1 and 2 weeks after the general population in England, with the gap widening to 6 weeks for younger migrants (16-29 years). Refugees specifically had a higher risk of a delayed second dose (odds ratio 1·75 [95 CI% 1·62-1·88]) and third dose (1·41 [1·31-1·53]). Older migrants (>65 years) were at least four times more likely to have not received their second or third dose compared with those of the same age in England. INTERPRETATION: Uptake of the first dose was slower across all age groups for migrants compared with the general population. Refugees and older migrants were more likely to have delayed uptake of COVID-19 vaccines and to not have received their second or third dose. Policymakers, researchers, and practitioners should consider how to best drive uptake of COVID-19 and other routine vaccine doses and understand and address personal and structural barriers to vaccination systems for diverse migrant populations. FUNDING: Wellcome Trust and UK Research and Innovation.

Making the invisible visible: using national surveillance data to identify people experiencing homelessness in England with COVID-19.

Persons experiencing homelessness (PEH) or rough sleeping are a vulnerable population, likely to be disproportionately affected by the coronavirus disease 2019 (COVID-19) pandemic. The impact of COVID-19 infection on this population is yet to be fully described in England. We present a novel method to identify COVID-19 cases in this population and describe its findings. A phenotype was developed and validated to identify PEH or rough sleeping in a national surveillance system. Confirmed COVID-19 cases in England from March 2020 to March 2022 were address-matched to known homelessness accommodations and shelters. Further cases were identified using address-based indicators, such as NHS pseudo postcodes. In total, 1835 cases were identified by the phenotype. Most were <39 years of age (66.8%) and male (62.8%). The proportion of cases was highest in London (29.8%). The proportion of cases of a minority ethnic background and deaths were disproportionality greater in this population, compared to all COVID-19 cases in England. This methodology provides an approach to track the impact of COVID-19 on a subset of this population and will be relevant to policy making. Future surveillance systems and studies may benefit from this approach to further investigate the impact of COVID-19 and other diseases on select populations.

A systematic review of the international evidence on the effectiveness of COVID-19 mitigation measures in communal rough sleeping accommodation.

BACKGROUND: Accommodations with shared washing facilities increase the risks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection for people experiencing rough sleeping and evidence on what interventions are effective in reducing these risks needs to be understood. METHODS: Systematic review, search date 6 December 2022 with methods published a priori. Electronic searches were conducted in MEDLINE, PubMed, Cochrane Library, CINAHL and the World Health Organization (WHO) COVID-19 Database and supplemented with grey literature searches, hand searches of reference lists and publication lists of known experts. Observational, interventional and modelling studies were included; screening, data extraction and risk of bias assessment were done in duplicate and narrative analyses were conducted. RESULTS: Fourteen studies from five countries (USA, England, France, Singapore and Canada) were included. Ten studies were surveillance reports, one was an uncontrolled pilot intervention, and three were modelling studies. Only two studies were longitudinal. All studies described the effectiveness of different individual or packages of mitigation measures. CONCLUSIONS: Despite a weak evidence base, the research suggests that combined mitigation measures can help to reduce SARS-CoV-2 transmission but are unlikely to prevent outbreaks entirely. Evidence suggests that community prevalence may modify the effectiveness of mitigation measures. More longitudinal research is needed. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021292803.

The impact of NHS charging regulations on healthcare access and utilisation among migrants in England: a systematic review.

BACKGROUND: The NHS Charges to Overseas Visitors Regulations 2015 outline when healthcare costs should be recuperated from overseas visitors in England. National and global stakeholders have expressed concerns that charging may exacerbate health inequalities and undermine public health efforts especially among vulnerable migrant groups. This review aims to systematically describe the evidence regarding the impact of NHS charging regulations on healthcare access and utilisation and health outcomes for migrants in England. METHODS: A systematic search of scientific databases and grey literature sources was performed. Quantitative and qualitative studies, case studies and grey literature published between 1 January 2014 and 1 April 2021 were included. Screening, data extraction and quality appraisal were carried out in accordance with PRISMA guidelines. RESULTS: From the 1,459 identified studies, 10 were selected for inclusion. 6 were qualitative, 3 were mixed methods and 1 was quantitative. The evidence is lacking but suggests that fears of charging and data sharing can deter some migrants from accessing healthcare. There is also evidence to suggest a lack of knowledge of the charging regulations among patients and healthcare professionals is contributing to this deterrence. CONCLUSIONS: Further independent research supported by strengthening of data collection is required to better understand the effects of charging on healthcare and health outcomes among vulnerable migrants. Our findings support improved training and communication about NHS Charging Regulations for patients and professionals.

A comparison of COVID-19 incidence rates across six European countries in 2021.

International comparisons of COVID-19 incidence rates have helped gain insights into the characteristics of the disease, benchmark disease impact, shape public health measures and inform potential travel restrictions and border control measures. However, these comparisons may be biased by differences in COVID-19 surveillance systems and approaches to reporting in each country. To better understand these differences and their impact on incidence comparisons, we collected data on surveillance systems from six European countries: Belgium, England, France, Italy, Romania and Sweden. Data collected included: target testing populations, access to testing, case definitions, data entry and management and statistical approaches to incidence calculation. Average testing, incidence and contextual data were also collected. Data represented the surveillance systems as they were in mid-May 2021. Overall, important differences between surveillance systems were detected. Results showed wide variations in testing rates, access to free testing and the types of tests recorded in national databases, which may substantially limit incidence comparability. By systematically including testing information when comparing incidence rates, these comparisons may be greatly improved. New indicators incorporating testing or existing indicators such as death or hospitalisation will be important to improving international comparisons.

Differential impact of quarantine policies for recovered COVID-19 cases in England: a case cohort study of surveillance data, June to December 2020.

BACKGROUND: From 12th March 2020, individuals in England were advised to quarantine in their home if a household member tested positive for SARS-CoV-2. A mandatory isolation period of 10 days was introduced on 28th September 2020 and applied to all individuals with COVID-19. We assessed the frequency, timing, and characteristics of recovered COVID-19 cases requiring subsequent quarantine episodes due to household re-exposure. METHODS: In this case cohort study, all laboratory-confirmed COVID-19 cases notified in England (29th June to 28th December 2020) were analysed to identify consecutive household case(s). Multivariable logistic regression was used to determine associations between case characteristics and need to quarantine following recent infection (within 28 days of diagnosis). RESULTS: Among 1,651,550 cases resident in private dwellings and Houses of Multiple Occupancy (HMOs), 744,548 (45.1%) were the only case in their home and 56,179 (3.4%) were succeeded by further household cases diagnosed within 11-28 days of their diagnosis. Of 1,641,412 cases arising in private homes, the likelihood of further household cases was highest for Bangladeshi (aOR = 2.20, 95% CI = 2.10-2.31) and Pakistani (aOR = 2.15, 95% CI = 2.08-2.22) individuals compared to White British, as well as among young people (17-24y vs. 25-64y; aOR = 1.19, 95% CI = 1.16-1.22), men (vs. women; aOR = 1.06, 95% CI = 1.04-1.08), London residents (vs. Yorkshire and Humber; aOR = 1.57, 95% CI = 1.52-1.63) and areas of high deprivation (IMD 1 vs. 10; aOR = 1.13, 95% CI = 1.09-1.19). CONCLUSION: Policies requiring quarantine on re-exposure differentially impact some of the most disadvantaged populations. Quarantine exemption for recently recovered individuals could mitigate the socioeconomic impact of responses to COVID-19 or similar infectious disease outbreaks.

Epidemiology of Confirmed COVID-19 Deaths in Adults, England, March-December 2020.

Of the 58,186 coronavirus deaths among adults in England during March-December 2020, 77% occurred in hospitals, 93% were in patients >60 years, and 91% occurred within 28 days of positive specimen. Cumulative mortality rates were highest among persons of Black, Asian, other, or mixed ethnicities and in socioeconomically deprived areas.

How Molecular Mobility, Physical State, and Drug Distribution Influence the Naproxen Release Profile from Different Mesoporous Silica Matrices.

Aiming to evaluate how the release profile of naproxen (nap) is influenced by its physical state, molecular mobility, and distribution in the host, this pharmaceutical drug was loaded in three different mesoporous silicas differing in their architecture and surface composition. Unmodified and partially silylated MCM-41 matrices, respectively MCM-41 and MCM-41sil, and a biphenylene-bridged periodic mesoporous organic matrix, PMOBph, were synthetized and used as drug carriers, having comparable pore sizes (∼3 nm) and loading percentages (∼30% w/w). The loaded guest was investigated by attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), and dielectric relaxation spectroscopy (DRS). DSC and XRD confirmed amorphization of a nap fraction incorporated inside the pores. A narrower glass transition was detected for PMOBph_nap, taken as an indication of the impact of host ordering, which also hinders the guest molecular mobility inside the pores as probed by DRS. While the PMOBph matrix is highly hydrophobic, the unmodified MCM-41 readily adsorbs water, accelerating the nap relaxation rate in the respective composite. In the dehydrated state, the faster dynamics was found for the silylated matrix since guest-host hydrogen bond interactions were inhibited to some extent by methylation. Nevertheless, in all the prepared composites, bulk-like crystalline drug deposits outside pores in a greater extent in PMOBph_nap. The DRS measurements analyzed in terms of conductivity show that, upon melting, nap easily migrates into pores in MCM-41-based composites, while it stays in the outer surface in the ordered PMOBph, determining a faster nap delivery from the latter matrix. On the other side, the mobility enhancement in the hydrated state controls the drug delivery in the unmodified MCM-41 matrix vs the silylated one. Therefore, DRS proved to be a suitable technique to disclose the influence of the ordering of the host surface and its chemical modification on the guest behavior, and, through conductivity depletion, it provides a mean to monitor the guest entrance inside the pores, easily followed even by untrained spectroscopists.

What do primary care staff know and do about blood borne virus testing and care for migrant patients? A national survey.

BACKGROUND: UK migrants born in intermediate to high prevalence areas for blood borne viruses (BBV) including hepatitis B, hepatitis C and HIV are at increased risk of these infections. National guidance from Public Health England (PHE) and National Institute for Health and Care Excellence (NICE) recommends primary care test this population to increase diagnoses and treatment. We aimed to investigate primary care professionals' knowledge of entitlements, and perceptions of barriers, for migrants accessing healthcare, and their policies, and reported practices and influences on provision of BBV testing in migrants. METHODS: A pre-piloted questionnaire was distributed between October 2017 and January 2018 to primary care professionals attending the Royal College of General Practitioners and Best Practice in Primary Care conferences, via a link in PHE Vaccine Updates and through professional networks. Survey results were analysed to give descriptive statistics, and responses by respondent characteristics: profession, region, practice size, and frequency of seeing migrant patients. Responses were considered on a per question basis with response rates for each question presented with the results. RESULTS: Four hundred fourteen questionnaires were returned with responses varying by question, representing an estimated 5.7% of English GP practices overall. Only 14% of respondents' practices systematically identified migrant patients for testing. Universal opt-out testing was offered to newly registering migrant patients by 18% of respondents for hepatitis B, 17% for hepatitis C and 21% for HIV. Knowledge of healthcare entitlements varied; fewer clinical staff knew that general practice consultations were free to all migrants (76%) than for urgent care (88%). Performance payment structure (76%) had the greatest reported influence on testing, followed by PHE and Clinical Commissioning Group recommendations (73% each). Language and culture were perceived to be the biggest barriers to accessing care. CONCLUSIONS: BBV testing for migrant patients in primary care is usually ad hoc, which is likely to lead to testing opportunities being missed. Knowledge of migrants' entitlements to healthcare varies and could affect access to care. Interventions to improve professional awareness and identification of migrant patients requiring BBV testing are needed to reduce the undiagnosed and untreated burden of BBVs in this vulnerable population.

Congenital Midline Cervical Cleft: A Variant of Tessier Number 30 Cleft Causing Micrognathia.

Congenital midline cervical cleft is a rare and generally isolated malformation of the ventral neck region with no clear etiology established. Mandibular deformities, such as micrognathia, could be considered as a consequence of a cleft cervical contracture. Complete surgical excision of the subcutaneous fibrous cord at an early age is the primary treatment modality, minimizing growth development problems on surrounding affected tissue. The aim of this study is to describe the clinical, surgical, and histological findings in a female child with congenital midline cervical cleft along with a relevant literature review. Three years follow-up after surgery exhibited satisfactory functional and cosmetic results.

Study of the Potential of Water Treatment Sludges in the Removal of Emerging Pollutants.

Presently, water quantity and quality problems persist both in developed and developing countries, and concerns have been raised about the presence of emerging pollutants (EPs) in water. The circular economy provides ways of achieving sustainable resource management that can be implemented in the water sector, such as the reuse of drinking water treatment sludges (WTSs). This study evaluated the potential of WTS containing a high concentration of activated carbon for the removal of two EPs: the steroid hormones 17ß-estradiol (E2) and 17α-ethinylestradiol (EE2). To this end, WTSs from two Portuguese water treatment plants (WTPs) were characterised and tested for their hormone adsorbance potential. Both WTSs showed a promising adsorption potential for the two hormones studied due to their textural and chemical properties. For WTS1, the final concentration for both hormones was lower than the limit of quantification (LOQ). As for WTS2, the results for E2 removal were similar to WTS1, although for EE2, the removal efficiency was lower (around 50%). The overall results indicate that this method may lead to new ways of using this erstwhile residue as a possible adsorbent material for the removal of several EPs present in wastewaters or other matrixes, and as such contributing to the achievement of Sustainable Development Goals (SDG) targets.

Perceptions of Portuguese parents about the acceptability of a multicomponent intervention targeted at behavioral inhibition during early childhood.

High and stable behavioral inhibition during early childhood is a risk factor for later anxiety disorders. The few available interventions targeted at behavioral inhibition have not yet been implemented in European countries. Evaluating intervention acceptability is essential when introducing interventions in new cultures. This study aimed to explore the perceptions of parents about the acceptability of the multicomponent Turtle Program in Portugal. Participants were 12 parents (from seven families) of children with a positive screening on the Behavioral Inhibition Questionnaire and no diagnoses of developmental disorders/selective mutism. Children's mean age was 55.86 months and most children were female and first-born. Parents and children participated in the eight-sessions Turtle Program. After each session, parents completed weekly satisfaction checklists. Following completion of the full intervention, parents were invited to participate in individual qualitative in-depth interviews. The thematic analysis revealed that both parents perceived the intervention objectives and contents as relevant. Both parents suggested the introduction of follow-up sessions, the discussion of practical experiences, the need to be sensitive to cultural differences in positive language, and the provision of more feedback about children's activities. These findings support prior research on the acceptability and cultural tailoring needed for parenting and child socioemotional learning interventions.

Una alta y estable conducta de inhibición durante la temprana niñez es un factor de riesgo para posteriores trastornos de ansiedad. Las pocas intervenciones disponibles que se enfocan en la inhibición de la conducta no se han implementado aún en países europeos. Evaluar el nivel de aceptación de la intervención es esencial cuando las intervenciones se introducen en nuevas culturas. Este estudio se propuso explorar las percepciones de los progenitores acerca del nivel de aceptación del multi-compuesto Programa Tortuga en Portugal. Los participantes fueron 12 progenitores (de siete familias) de niños con una positiva detección en el Cuestionario de Inhibición de la Conducta y sin diagnóstico de trastornos de desarrollo/mutismo selectivo. La edad promedio de los niños fue 55.86 meses y la mayoría eran niñas y primogénitas. Los progenitores y los niños participaron en las ocho sesiones del Programa Tortuga. Después de cada sesión, los progenitores completaron listas semanales de chequeo de la satisfacción. Luego de completar la intervención en su totalidad, se invitó a los progenitores a participar en entrevistas cualitativas individuales para profundizar. Los análisis temáticos revelaron que ambos progenitores percibieron como relevantes los objetivos y el contenido de la intervención. Ambos progenitores sugirieron introducir sesiones de seguimiento, la discusión de experiencias prácticas, la necesidad de mostrarse sensible a las diferencias culturales en lenguaje positivo y la provisión de más información sobre las actividades de los niños. Estos resultados apoyan la investigación anterior sobre el nivel de aceptación y la adaptación cultural necesarias en las intervenciones sobre la crianza y el aprendizaje socioemocional del niño.

L'inhibition comportementale élevée et stable durant la petite enfance est un facteur de risque pour des troubles de l'anxiété plus tard. Quelques interventions disponibles ciblant l'inhibition comportementale n'ont pas encore été mises en œuvre dans les pays européens. Evaluer l'acceptabilité de l'intervention est essentiel lorsqu'on introduit des interventions dans de nouvelles cultures. Cette étude s'est donnée pour but d'explorer les perceptions des parents à propos de l'acceptabilité du Programme Tortue à composants multiples au Portugal. Les participants ont consisté en 12 parents (de sept familles) d'enfants ayant eu un dépistage positif au Questionnaire d'Inhibition Comportementale et aucun diagnostic de troubles développementaux / mutisme sélectif. L'âge moyen des enfants était de 55,86 mois et la plupart des enfants étaient des filles et des premières nées. Les parents et les enfants ont participé au Programme Tortue de huit séances. Après chaque séance les parents ont rempli des checklists de satisfaction hebdomadaires. Après avoir terminé l'intervention totale les parents ont été invité à participer à des entretiens individuels en profondeur et qualitatifs. L'analyse thématique a révélé que les deux parents percevaient les objectifs d'intervention et les contenus comme étant pertinents. Les deux parents ont suggéré l'introduction de séances de suivi, la discussion d'expériences pratiques, le besoin d'être sensible aux différences culturelles dans le langage positif et le besoin de plus de commentaires sur les activités des enfants. Ces résultats soutiennent les recherches précédentes sur l'acceptabilité et l'adaptation culturelle nécessaire pour le parentage et les interventions pour le développement socioémotionnel de l'enfant.

Shifting determinants of health inequalities in unstable times: Portugal as a case study.

Background: We explore how health inequalities (HI) changed in Portugal over the last decade, considering it is one of the most unequal European countries and has gone through major economic changes. We describe how inequalities in limitations changed considering different socioeconomic determinants, in order to understand what drove changes in HI. Methods: We used cross-sectional waves from the European Survey on Income and Living Conditions database to determine how inequalities in health limitations changed between 2004 and 2014 in Portugal in residents aged 16 years and over. We calculated prevalence estimates of limitations and differences between income terciles, the concentration index for each year and its decomposition and multiple logistic regressions to estimate the association between socioeconomic determinants and limitations. Results: The prevalence of health limitations increased in Portugal since 2004, especially after 2010, from 35 to 47%. But the difference between top and bottom income terciles decreased from 23 to 10 percentage points, as richer people experienced a steeper increase. This was driven by an increase in prevalence among economically active people, who, from 2011 onwards, had more limitations (OR and 95% CI were 2.42 [2.13-2.75] in 2004 and 0.71 [0.65-0.78] in 2014). Conclusion: These results suggest worsening health in Portugal in the last decade, possibly connected to periods of economic instability. However, absolute HI decreased considerably in the same period. We discuss the possible role of diverse adaptation capacity of socioeconomic groups, and of high emigration rates of young, healthier people, reflecting another side of the 'migrant health effect'.

Recovery of phenolic compounds from multi-component solution by a synthesized activated carbon using resorcinol and formaldehyde.

The adsorption of four phenolic compounds (gallic acid, protocatechuic acid, vanillic acid and syringic acid) is investigated using a synthesized mesoporous carbon on both single and multi-component synthetic solutions. Some correlation of the adsorption capacity of the carbon and the nature of adsorbate could be made, except for gallic acid whose concentration decrease seems to be not exclusively due to adsorption but also to polymerization reaction. In the multi-component mixture, negative effects in the adsorption capacity are observed probably due to competition for the active centers of the adsorbent surface. In desorption studies, ethanol presents better performance than water and acetonitrile. Vanillic acid is the compound with the higher adsorption and interestingly it is then possible to desorb a relatively high amount of it from the adsorbent, which may represent a possibility for a selective recovery of vanillic acid. These results present a potential way to treat the wastewater from the cork industry.

Connecting the dots on health inequalities--a systematic review on the social determinants of health in Portugal.

INTRODUCTION: Health inequalities are recognised as a public health issue worldwide, but only a few countries have developed national strategies to monitor and reduce them. Despite its considerable health inequalities, Portugal seems to lack a systematic strategy to tackle them, possibly due to the absence of organised evidence on the issue. We performed a systematic review that aimed to describe the available evidence on social inequalities in health in Portugal, in order to contribute towards a comprehensive and focused strategy to tackle them. METHODS: We followed the PRISMA guidelines and searched Scopus, Web of Science and PubMed for studies that looked at the association between a measure of socioeconomic status and a health outcome in the Portuguese resident population since the year 2000. We excluded health behaviours and healthcare use from our search. We performed a qualitative description of the results. RESULTS: Seventy-one publications were selected, all reporting observational analyses, most of them using cross-sectional data. These publications showed strong evidence for health inequalities related to education and gender, chiefly for obesity, self-rated health and mental health. CONCLUSIONS: Analysis of the eligible publications showed that current research does not seem to have consistently covered the link between health and key Portuguese social problems. A strategy focusing on the monitoring of most prevalent diseases, most determining socioeconomic factors and vulnerable populations would be crucial to guide academic research in a country in which health inequalities are so ubiquitous and deeply rooted. REGISTRATION: This systematic review is not registered.

The 'dark side' of social capital: trust and self-rated health in European countries.

BACKGROUND: Generalized interpersonal trust (as an indicator of social capital) has been linked to health status at both the individual and ecological level. We sought to examine how changes in contextual and individual trust are associated with changes in self-rated health in the European Social Surveys 2002-12. METHODS: A multilevel analysis using a variance components model was performed on 203 452 individuals nested within 145 country cohorts covering 35 countries. Conditional on sociodemographic covariates, we sought to examine the association between self-rated health and individual trust, country average trust and a cross-level interaction between the two. RESULTS: Although individual trust perceptions were significantly correlated with self-rated health [OR = 0.95, 95% confidence interval (0.94-0.96)], country-level trust was not associated [OR = 1.12, 95% confidence interval (0.95-1.32)]. There was, however, a strong crosslevel interaction between contextual and individual trust (P < 0.001), such that individuals with high interpersonal trust reported better health in contexts in which other individuals expressed high average interpersonal trust. Conversely, low trust individuals reported worse health in high trust contexts. CONCLUSION: Our findings suggest that contexts with increasing average trust can be harmful for low trust individuals, which might reflect the negative impact that social capital can have in certain groups. These findings suggest that contextual trust has a complex role in explaining health inequalities and individual self-rated health.

Treml4, an Ig superfamily member, mediates presentation of several antigens to T cells in vivo, including protective immunity to HER2 protein.

Members of the triggering expressed on myeloid cells (Trem) receptor family fine-tune inflammatory responses. We previously identified one of these receptors, called Treml4, expressed mainly in the spleen, as well as at high levels by CD8α(+) dendritic cells and macrophages. Like other Trem family members, Treml4 has an Ig-like extracellular domain and a short cytoplasmic tail that associates with the adaptor DAP12. To follow up on our initial results that Treml4-Fc fusion proteins bind necrotic cells, we generated a knockout mouse to assess the role of Treml4 in the uptake and presentation of dying cells in vivo. Loss of Treml4 expression did not impair uptake of dying cells by CD8α(+) dendritic cells or cross-presentation of cell-associated Ag to CD8(+) T cells, suggesting overlapping function between Treml4 and other receptors in vivo. To further investigate Treml4 function, we took advantage of a newly generated mAb against Treml4 and engineered its H chain to express three different Ags (i.e., OVA, HIV GAGp24, and the extracellular domain of the breast cancer protein HER2). OVA directed to Treml4 was efficiently presented to CD8(+) and CD4(+) T cells in vivo. Anti-Treml4-GAGp24 mAbs, given along with a maturation stimulus, induced Th1 Ag-specific responses that were not observed in Treml4 knockout mice. Also, HER2 targeting using anti-Treml4 mAbs elicited combined CD4(+) and CD8(+) T cell immunity, and both T cells participated in resistance to a transplantable tumor. Therefore, Treml4 participates in Ag presentation in vivo, and targeting Ags with anti-Treml4 Abs enhances immunization of otherwise naive mice.